Operative Treatment of Intramedullary Hematoma Associated with Congenital Deficiency of &agr;2-Plasmin Inhibitor. A Report of Three Cases*

Congenital deficiency of a2-plasmin inhibitor is a very rare disease that is associated with severe bleeding problems. To our knowledge, the condition was first reported in 1978 by Koie et al., who described a twentyfive-year-old man who had symptoms similar to those of severe hemophilia. Since then, the cases of at least eight patients, from six families, who had homozygous deficiency have been reported'-. The main symptoms were umbilical bleeding, bleeding in the central nervous system, epistaxis, bleeding gums, hemothorax, hypermenorrhea, hemarthrosis, and excessive loss of blood after minor trauma. These patients often needed to be hospitalized for long periods because of the tendency for severe bleeding that had begun in early childhood and was clinically similar to hemophilia. The episodes of bleeding were thought to be characterized by hemostatic plugs that had formed normally but disappeared rapidly because of unrestrained fibrinolysis. Thus, routine laboratory studies revealed no important abnormality of coagulation or platelet function except the shortened times of lysis of whole blood and euglobulin. The diagnosis usually was made on the basis of assay of the level of antigen or the activity of a2-plasmin inhibitor. We first reported multiple intramedullary hematomas, a form of bleeding, in 1991. This condition developed in the long bones of three sisters who had a congenital deficiency of a2-plasmin inhibitor. The episodes of bleeding in these sisters were described in that report and in a previous one. The long-term clinical features of the lesions and the results of successful operative treatment are described in the present report. The concentration of a2-plasmin inhibitor in the plasma of these patients was assayed with functional and immunological methods, and it was found to be severely deficient. The genetic abnormality was shown to be a frame-shift mutation, leading to elongation